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2018 ; 9
(ä): 504
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Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition
of Effector CD4(+) and CD8(+) T-Cell Responses
#MMPMID29662488
Vendomèle J
; Dehmani S
; Khebizi Q
; Galy A
; Fisson S
Front Immunol
2018[]; 9
(ä): 504
PMID29662488
show ga
PURPOSE: Injection of an antigen into the anterior chamber of the eye induces a
peripheral antigen-specific immune modulation mechanism, known as anterior
chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity
experiments argue that the subretinal space (SR) of the eye displays properties
similar to ACAID. However, no investigation was performed regarding the
differential impact of a subretinal antigen injection on peripheral CD4(+) versus
CD8(+) T cells, on the potential immune deviation regarding Th profiles, and on
the antigen-specificity of the inhibition. A better understanding of these
mechanisms is crucial to improve safety and immunomonitoring of ongoing
therapeutic approaches targeting the SR. The aim of this study is to characterize
the proliferative capacities and cytokine patterns of antigen-specific CD4(+) and
CD8(+) T cells after a subretinal injection of antigen in mice. METHODS:
Ubiquitously Transcribed tetratricopeptide repeat gene Y-linked (UTY) and DEAD
Box polypeptide 3 Y-linked (DBY) peptides which respectively include MHCI- and
MHCII-restricted T-cell epitopes of the mouse HY male antigen, were injected into
the subretinal space of C57BL/6 female mice. 2?weeks later, these mice were
immunized subcutaneously with these peptides and compared to control mice. A week
later, T-cell immune responses were analyzed by IFN? ELISpot assays and cytokine
measurements (IL-2, IL-4, IL-6, IL-10, IL-13, IL-17a, IFN?, TNF?, GM-CSF, and
MCP-1) in the spleen and with proliferation assays in draining lymph nodes.
RESULTS: Immune cells from mice that received HY peptides in the SR before
immunization, compared with those from control immunized mice, secreted
significantly smaller quantities of Th1/Tc1, Th2/Tc2, and Th17/Tc17 cytokines,
and HY-specific CD4(+) T cells proliferated less in response to HY peptides.
CONCLUSION: Taken together, our data clearly demonstrate that the subretinal
injection of HY peptides induces a systemic HY-specific inhibition of
conventional Th profiles and CD8(+) T cells. We propose to call this phenomenon
SRAII, for subretinal-associated immune inhibition.